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Alterations in perivascular innervation function in mesenteric arteries from offspring of diabetic rats
D B de Queiroz1, E Sastre2,3, L Caracuel2,3
1Departamento de Fisiologia e Farmacologia, Universidade Federal de Pernambuco, Recife, Brazil.
Insights
Maternal diabetes increases offspring blood pressure via enhanced sympathetic and nitrergic nerve activity in the superior mesenteric artery. This heightened innervation contributes to elevated vascular tone and hypertension in offspring.
Area of Science:
- Cardiovascular Physiology
- Developmental Biology
- Endocrinology
Background:
- Maternal diabetes is linked to increased blood pressure in adult offspring.
- The underlying mechanisms, particularly vascular innervation, remain unclear.
Purpose of the Study:
- To investigate the role of perivascular sympathetic and nitrergic innervation in the superior mesenteric artery (SMA) of offspring exposed to a diabetic intrauterine environment.
- To determine if altered innervation contributes to elevated blood pressure in these offspring.
Main Methods:
- Diabetes induced in pregnant Wistar rats using streptozotocin.
- Vascular responses and neurotransmitter/NO release studied in SMA segments from offspring of control and diabetic rats.
- Sympathetic and nitrergic nerve densities assessed via immunofluorescence.
Main Results:
- Offspring of diabetic rats (O-DR) exhibited higher blood pressure and enhanced electrical field stimulation-induced vasoconstriction in SMA.
- Increased norepinephrine (NA), adenosine triphosphate (ATP), and nitric oxide (NO) release observed in O-DR SMA.
- Phosphorylated neuronal nitric oxide synthase (P-nNOS) expression was elevated in O-DR, despite similar nNOS expression and nerve densities.
Conclusions:
- Sympathetic and nitrergic nerve activity is upregulated in the SMA of offspring from diabetic mothers.
- This enhanced innervation contributes to increased vasoconstriction and may play a role in the elevated blood pressure observed in these offspring.
Background And Purpose:
We have reported that exposure to a diabetic intrauterine environment during pregnancy increases blood pressure in adult offspring, but the mechanisms involved are not completely understood. This study was designed to analyse a possible role of perivascular sympathetic and nitrergic innervation in the superior mesenteric artery (SMA) in this effect.
Experimental Approach:
Diabetes was induced in pregnant Wistar rats by a single injection of streptozotocin. Endothelium-denuded vascular rings from the offspring of control (O-CR) and diabetic rats (O-DR) were used. Vasomotor responses to electrical field stimulation (EFS), NA and the NO donor DEA-NO were studied. The expressions of neuronal NOS (nNOS) and phospho-nNOS (P-nNOS) and release of NA, ATP and NO were determined. Sympathetic and nitrergic nerve densities were analysed by immunofluorescence.
Key Results:
Blood pressure was higher in O-DR animals. EFS-induced vasoconstriction was greater in O-DR animals. This response was decreased by phentolamine more in O-DR animals than their controls. L-NAME increased EFS-induced vasoconstriction more strongly in O-DR than in O-CR segments. Vasomotor responses to NA or DEA-NO were not modified. NA, ATP and NO release was increased in segments from O-DR. nNOS expression was not modified, whereas P-nNOS expression was increased in O-DR. Sympathetic and nitrergic nerve densities were similar in both experimental groups.
Conclusions And Implications:
The activity of sympathetic and nitrergic innervation is increased in SMA from O-DR animals. The net effect is an increase in EFS-induced contractions in these animals. These effects may contribute to the increased blood pressure observed in the offspring of diabetic rats.
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